Our interest is in understanding the contribution of Epstein-Barr Virus to soft tissue pathologies of the oral cavity, particularly oral leukoplakias. Hairy leukoplakia (HLP) is a recently described lesion that develops on the lateral tongue borders of patients who are immunocompromised. This lesion may serve as a source of infectious particles that have the potential to reinfect other cells and contribute to pathogenesis. We are also interested in identifying if there is a role for EBV in the development and progression of tobacco associated lesions. The objective in the study of Hairy Leukoplakia has been to utilize RT PCR to characterize gene expression at the mRNA level. Biopsy treated specimens of lateral tongue were processed and Dnase treated. CDNA was synthesized and Polymerase Chain Reaction was performed using known primers that amplify across introns. This technique identifies the pattern of alternate splicing that may occur. Various lytic and latent cycle genes have been detected and novel forms of transcription have been identified in this lesion. Western blot analysis will be performed to determine gene expression at the protein level. Expression of the CD21 receptor has been identified in several samples. This receptor has been described as a means of viral entry in lymphoid cells. The receptor has been sequenced from HLP and an epithelial cell line that has been transfected with CD21 is being established. An attempt will be made to infect these cell lines with HLP lysates. This invitro system will enable the study of the molecular pathogenesis of EBV in epithelial cells.